Coated polyunsaturated fatty acid-containing particles and coated liquid pharmaceutical-containing particles

ABSTRACT

A process for coating a polyunsaturated fatty acid (PUFA)-containing carrier particle or a PUFA matrix particle, or a liquid pharmaceutical-containing carrier particle or a liquid pharmaceutical matrix particle. Also disclosed are such particles made by the process of the invention and foods, pharmaceuticals, beverages, nutritional supplements, infant formula, pet food and animal feed with incorporate such particles.

This application claims the benefit of U.S. Provisional Application No.60/403598, filed Aug. 14, 2002.

FIELD OF THE INVENTION

This invention is in the field of particle coating, specifically,coating of polyunsaturated fatty acid containing particles and coatingof liquid pharmaceutical-containing particles. The coated products areuseful in the pharmaceutical, nutriceutical and food industries.

BACKGROUND OF THE INVENTION

There is a need in the art for a means of economically handling,preserving, delivering and measuring liquids, both aqueous andnonaqueous liquids such as food oils and pharmaceuticals, in manycommercial applications including in the food and pharmaceuticalindustries. One such currently employed method involves the coating ofliquids onto small particles, which particles, optimally, retain thestability and handling characteristics of solid flowable powders.Further, liquids processed into solid powder form have been found to beless susceptible to deterioration through excessive temperature,volatilization or reaction with oxygen. The particles that are coatedmay be carrier particles or active particles. Active particles generallyare those that will be part of the desired material to be delivered.Carrier particles generally are those that are relatively inert in thesense that they are not part of the desired material to be delivered.

One example of an “active” particle is one that is comprised of a liquidpharmaceutically-active material. A further example of an activeparticle is one that is comprised of polyunsaturated fatty acids (PUFA).The human body is capable of producing most of the fatty acids which itrequires to function. Two polyunsaturated fatty acids, eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA), however, cannot besynthesized efficiently by the human body and, thus, have to be suppliedthrough the diet. Since the human body cannot produce adequatequantities of these polyunsaturated fatty acids, they are calledessential fatty acids.

Two main families of PUFAs are the omega-3 fatty acids and the omega-6fatty acids. EPA and DHA are very important omega-3 fatty acids. Fishoil is known to be one of the best sources of these omega-3 fatty acids.PUFAs are important components of the plasma membrane of the cell, wherethey may be found in such forms as phospholipids. PUFAs are necessaryfor proper development, particularly in the developing infant brain, andfor tissue formation and repair. PUFAs also serve as precursors to othermolecules of importance in human beings and animals, including theprostacyclins, eicosanoids, leukotrienes and prostaglandin.

Four major long chain PUFAs of importance include DHA and EPA which areprimarily found in different types of fish oil, gamma-linolenic acid(GLA) which is found in the seeds of a number of plants, includingevening primrose (Oenothera biennis), borage (Borago officinalis) andblack currants (Ribes nigrum), and stearidonic acid (SDA), which isfound in marine oils and plants seeds. Both GLA and another importantlong chain PUFA, arachidonic acid (ARA), are found in filamentous fungi.ARA can be purified from animal tissues including liver and adrenalgland. GLA, ARA, EPA and SDA are themselves, or are dietary precursorsto, important long chain fatty acids involved in prostaglandinsynthesis, in treatment of heart disease, and in development of braintissue.

Research has shown that omega-3 fatty acids reduce the risk of heartdisease as well as having a positive effect on children's development.Results have been disclosed indicating the positive effect of thesefatty acids on certain mental illnesses, autoimmune diseases and jointcomplaints. Thus, there are many health benefits associated with a dietsupplemented with these fatty acids.

Unfortunately, PUFAs are very susceptible to oxidation due to the highdegree of unsaturation. When oxidized, the fatty acids turn rancidproducing an unpleasant smell and taste. This means that for PUFAs to beincorporated into food components, they have to be protected againstoxidation. The coating of these materials affords protection to theseingredients and allows them to be delivered at the target site at therequired time. Shelf-life and stability of PUFAs is improved due to theinhibition of oxidation. Other benefits of coating include the ease ofhandling of the material(s) due to the small particulate, powder form ofthe coated PUFA-containing material or coated PUFA matrix particle andthe suitability for incorporation at any of a variety of stages ofpreparation of many differing types of foodstuffs and nutritionalcompositions.

Microencapsulation has been defined as a process by which smallparticles (generally between 1 to 1000 microns in diameter) of solid,liquid or gas are packaged within a secondary material to form amicrocapsule. (Sanguansri et al., Microencapsulation for InnovativeIngredients A Scoping Study: Opportunities for Research into theMicroencapsulation of Food Ingredients, Food Science Australia, May2001).

Vasishtha, Prepared Foods, “Microencapsulation: Delivering a marketadvantage (July 2002) provides an overview of the types of core andcoating materials and encapsulation techniques used in the industry. Avariety of encapsulation processes are mentioned and include bothphysical and chemical techniques. Examples of physical techniquesmentioned are spray-drying, the spinning disc and coextrusion processes.Examples of chemical techniques mentioned are phase separation, gelationand coacervation.

U.S. Pat. No. 6,048,557, issued to Van Den Berg et al. on Apr. 11, 2002,describes PUFA encapsulated solid carrier particle for use as afoodstuff. Specifically, solid carrier particles are provided on towhich have been encapsulated, or absorbed, at least one PUFA in a liquidform.

WO 01174175, published Oct. 11, 2001, described encapsulation of foodingredients, in particular, oxygen sensitive oils or oil solubleingredients.

U.S. Pat. No. 4,895,725, issued to Kantor et al. on Jan. 23, 1990,describes microencapsulation of fish oils which are formed by preparingan emulsion of an oil-based biologically active compound and a non-oilsoluble enteric coating in a basic solution, atomizing the emulsion intoan acidic aqueous solution, and separating the precipitatedmicrocapsules from the acidic aqueous solution.

U.S. Pat. No. 6,234,464 B1, issued to Krumbholz et al. on May 22, 2001,describes microencapsulated unsaturated fatty acid or fatty acidcompound or mixture thereof involving two layers. The inner layer iscomposed of gelatin A, gelatin B, casein or an alginate or of aderivative or salt of one of these polymers. The outer layer is composedof gelatin B, gum arabic, pectin or chitosan or a derivative or salt ofone of these polymers.

U.S. Pat. No. 4,217,370, issued to Rawlings et al. on Aug. 12, 1980,describes lipid-containing feed supplements and foodstuffs made byadmixing a lipid material to form an emulsion and adjusting the pH tolower it to its isoelectric point, thereby aggregating the protein andsimultaneously microencapsulating the lipid.

U.S. Pat. No. 5,087,461, issued to Levine et al. on Feb. 11, 1992,describes a spray-dried composition comprising at least one volatilecomponent in a carrier and in the form of an amorphous powder, isfurther encapsulated in a glassy matrix formed from a mixture of fourdifferent carbohydrates.

An apparatus and process for coating small solid particles, such aspowdery or granular materials, are described in WO 97/07879 publishedMar. 6, 1997 and assigned to E. I. du Pont de Nemours and Company. Thisprocess involves metering a liquid composition comprising a coatingmaterial, where the liquid composition is either a solution, slurry ormelt, into a flow restrictor and injecting a gas stream through the flowrestrictor concurrently with the metering of the liquid composition tocreate a zone of turbulence at the outlet of the flow restrictor,thereby atomizing the liquid composition. The gas stream is heated priorto injecting it through the flow restrictor. A solid particle is addedto the zone of turbulence concurrently with the metering of the liquidcomposition and the injection of the heated gas to mix the solidparticle with the atomized liquid composition. The mixing at the zone ofturbulence coats the solid particle with the coating material.

WO 97/07676 to E. I. du Pont de Nemours and Company discloses theapparatus of WO 97/07879, along with the use of the apparatus in aprocess for coating crop protection solid particles. Coatings arewater-insoluble, and coating thicknesses are represented by weightpercent rather than thickness.

U.S. Pat. No. 6,015,773, issued to Wysong et al. on Jan. 18, 2000,describes a crop protection composition comprising a mononucleate cropprotection solid particle coated with water-insoluble coating materialhaving a diameter in the range from 0.5 to 50 micrometers. Thiscomposition is made by a process which results in substantialnon-agglomeration of the coated particles.

Applicants' assignee's copending application having application Ser. No.10/174687, filed Jun. 19, 2002 and having Attorney Docket Number CL-1879US NA discloses a process for dry coating a food particle having itslargest diameter in the range from 0.5 mm to 20.0 mm with a liquidcoating material. The coated food particle has a moisture level that issubstantially the same as the moisture level of the uncoated foodparticle. Also disclosed is a process for coating a frozen liquidparticle having a size in the range from 5 micrometers to 5 millimeterswith a liquid coating material.

Applicants' assignees' copending, concurrently filed herewithprovisional applications having Attorney Docket numbers CL2101, CL2149,CL2150, CL2178 and PTI sp1255 disclose subject matter related to thepresent application, and are specifically incorporated herein byreference.

U.S. Pat. No. 6,224,939 B1 issued to Cherukuri et al May 1, 2002describes a method an apparatus for the coating of feedstock, wherein asolid matrix additive is spray injected in a free-flow condition.

U.S. Pat. Nos. 3,241,520 and 3,253,944 disclose a particle coatingmethod wherein relatively large pellets, granules and particles aresuspended in a stream of air while coating material in a liquid form ismixed with the particles.

Shahidi et al., Critical Reviews in Food Science and Nutrition, 33(6):501-547 (1993) presents a review of the art of microcoating of foodingredients.

U.S. Pat. No. 4,848,673, issued to Masuda et al. on Jul. 18, 1989,describes a fluidized granulating and coating apparatus and method arerecirculated through the treating vessel to ensure high stability of thegranulating and coating operation.

SUMMARY OF THE INVENTION

The present invention includes a process for coating a polyunsaturatedfatty acid (PUFA)-containing carrier particle or a PUFA matrix particle,the process comprising the steps of:

-   -   (a) metering a liquid coating material through a flow        restrictor;    -   (b) injecting a gas stream through the flow restrictor        concurrently with step (a) to (i) atomize the liquid coating        material and (ii) create turbulent flow of the gas stream and        the atomized liquid coating material, wherein the gas stream is        optionally heated; and    -   (c) adding a PUFA-containing carrier particle or a PUFA matrix        particle to the turbulent flow region concurrently with        steps (a) and (b), wherein the PUFA-containing carrier particle        or the PUFA matrix particle mixes with the atomized liquid        coating material to provide an coated PUFA-containing carrier        particle or a PUFA matrix particle.

The present invention further includes a process for coating a liquidpharmaceutical-containing carrier particle or a liquid pharmaceuticalmatrix particle, the process comprising the steps of:

-   -   (a) metering a liquid coating material through a flow        restrictor;    -   (b) injecting a gas stream through the flow restrictor        concurrently with step (a) to (i) atomize the liquid coating        material and (ii) create turbulent flow of the gas stream and        the atomized liquid coating material, wherein the gas stream is        optionally heated; and    -   (c) adding a liquid pharmaceutical-containing carrier particle        or a liquid pharmaceutical matrix particle to the turbulent flow        region concurrently with steps (a) and (b), wherein the liquid        pharmaceutical-containing carrier particle or the liquid        pharmaceutical matrix particle mixes with the atomized liquid        coating material to provide an coated pharmaceutical-containing        carrier particle or a pharmaceutical matrix particle.

This invention can be practiced with carrier particles selected from thenonexhaustive group consisting of a protein, fumed silica, titaniumdioxide, calcium carbonate, a carbohydrate, a food particle, minerals,salts, lipids, antioxidants, a solid pharmaceutical particle, or anysolid particle capable of being loaded with a PUFA or a liquidpharmaceutical.

As used by Applicants for purposes of this disclosure, pharmaceuticalscan be considered to include, but are not limited to, nutraceuticals,vitamins, supplements, minerals, enzymes, probiotics, bronchodilators,anabolic steroids, analeptics, analgesics, proteins, peptides,antibodies, vaccines, anesthetics, antacids, antihelmintics,anti-arrthymics, antibiotics, anticoagulants, anticolonergics,anticonvulsants, antidepressants, antidiabetics, antidiarrheals,anti-emetics, anti-epileptics, antihistamines, antihormones,antihypertensives, anti-inflammatories, antimuscarinics, antimycotics,antineoplastics, anti-obesity drugs, antiprotozoals, antipsychotics,antispasmotics, anti-thrombics, antithyroid drugs, antitussives,antivirals, anxiolytics, astringents, beta-adrenergic receptor blockingdrugs, bile acids, bronchospasmolytic drugs, calcium channel blockers,cardiac glycosides, contraceptives, corticosteriods, diagnostics,digestives, diuretics, dopaminergics, electrolytes, emetics, haemostaticdrugs, hormones, hormone replacement therapy drugs, hypnotics,hypoglycemic drugs, immunosuppressants, impotence drugs, laxatives,lipid regulators, muscle relaxants, pain relievers,parasympathicolytics, parasympathicomimetics, prostagladins,psychostimulants, sedatives, sex steroids, spasmolytics, sulfonamides,sympathicolytics, sympathicomimetics, sympathomimetics, thyreomimetics,thyreostatic drugs, vasodialators, and xanthines. Many suchpharmaceuticals can be formulated into solid carrier particles or solidmatrix particles, suitable for being loaded with a liquid pharmaceuticalor PUFA, and then subsequently coated by the process of the invention.Regarding the process of loading liquid pharmaceutical materials ontosolid carrier particles or porpous matrix particles, Applicantsspecifically incorporate by reference herein the concurrently-filed andco-owned application having attorney docket number CL2178 and entitled:Process for Coating a Pharmaceutical Particle”. Further, one skilled inart of coating will realize that the process for coating the liquidpharmaceutical carrier of matrix particle or the PUFA matrix or carrierarticle can be used for the initial loading of the PUFA material orliquid pharmaceutical material onto the porous matrix or solid carrierparticle.

The term “liquid pharmaceutical” or “pharmaceutical liquid” refers toany pharmaceutically active ingredient existing in a physically liquidform, including in the form of an emulsion, a suspension, a dispersion,an oil or a solution.

The pharmaceutical particles formulated by the claimed processes aresuitable for delivery to mammals by a variety of routes ofadministration including, for example, oral, inhalable, transdermal,parenteral, buccal, nasal, vaginal, rectal, sub-lingual, ocular,periodontal, implantation, or topical.

In a second embodiment the process of the invention relating to coatingPUFA matrix or carrier particles or liquid pharmaceutical matrix orcarrier particles can be practiced by repeating steps (a)-(c) at leastonce wherein the liquid coating material is the same or different orrepeating steps (a)-(c) at least once using a liquid coating materialwhich can be the same or different from the first liquid coatingmaterial.

In a further embodiment, this invention includes a coatedPUFA-containing carrier particle or coated PUFA matrix particle made bythe claimed process.

In a further embodiment, this invention includes a coated liquidpharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process.

In a further embodiment, this invention includes a food comprising acoated PUFA-containing carrier particle or coated PUFA matrix particlemade by the claimed process, or a food comprising a coated liquidpharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process.

In a further embodiment, this invention includes a nutritionalsupplement comprising a coated PUFA-containing carrier particle orcoated PUFA matrix particle made by the claimed process, or anutritional supplement comprising a coated liquidpharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process

In a further embodiment, this invention includes a beverage comprising acoated PUFA-containing carrier particle or coated PUFA matrix particlemade by the claimed process, or a beverage comprising a coated liquidpharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process

In a further embodiment, this invention includes infant formulacomprising a coated PUFA-containing carrier particle or coated PUFAmatrix particle made by the claimed process, or infant formulacomprising a coated liquid pharmaceutical-containing carrier particle orcoated liquid pharmaceutical matrix particle made by the claimed process

In a further embodiment, this invention includes a pet food comprising acoated PUFA-containing carrier particle or coated PUFA matrix particlemade by the claimed process, or a pet food comprising a coated liquidpharmaceutcal-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process

In a further embodiment, this invention includes animal feed comprisinga coated PUFA-containing carrier particle or coated PUFA matrix particlemade by the claimed process, or an animal feed comprising a coatedliquid pharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process

In a further embodiment, this invention includes the use of a coatedPUFA-containing carrier particle or coated PUFA matrix particle made bythe claimed process in producing a product selected from the groupconsisting of a food, nutritional supplement beverage, infant formula, adairy product, a pet food or animal feed.

In a further embodiment, this invention includes the use of a coatedliquid pharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the claimed process in producinga product selected from the group consisting of a food, nutritionalsupplement beverage, infant formula, a dairy product, a pet food oranimal feed.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic diagram of a portion of the apparatus inaccordance with the present invention.

FIG. 2 is a cut away, expanded, cross-sectional view of a portion of theapparatus show in FIG. 1.

FIG. 3 depicts an alternate configuration of the apparatus shown inFIGS. 1 and 2.

DETAILED DESCRIPTION OF THE INVENTION

All patents, patent applications and publications referred to herein areincorporated by reference in their entirety.

In the context of this disclosure, a number of terms shall be utilized.

The term “polyunsaturated fatty acid” or “PUFA” as used herein refers tofatty acids that contain two or more double bounds. There are two mainfamilies of PUFAs, the omega-3 and omega-6 families. The omega-3 fattyacids are those with their endmost double bond 3 carbons from theirmethyl end. The omega-6 fatty acids are those with their endmost doublebond 6 carbon atoms from their methyl end.

Humans cannot efficiently synthesize fatty acids with double bondslocated at position 6 or lower in the hydrocarbon chain (whendesignating position with reference to the methyl end of the fatty acylchain), e.g., linoleic and linolenic acids. As such, these PUFAs areconsidered to be “essential fatty acids” in the diet. Fatty acidssynthesized from linoleic and linolenic acids, such as arachidonic andeicosapentaenoic and docosahexaenoic acids, are by analogy alsoessential fatty acids and must be obtained via the diet. All essentialfatty acids are polyunsaturated.

The term “PUFA-containing carrier particle” or“pharmaceutical-containing carrier particle” refers to any carrierparticle onto which at least one PUFA or pharmaceutical liquid has beenadsorbed or at least one PUFA or pharmaceutical liquid has been loaded.

The term “PUFA matrix particle” or “pharmaceutical matrix particle”refers to any type of matrix particle including but not limited tomulticore particles, core shell particles, capsules, etc. which containsor incorporates at least one PUFA, or one pharmaceutically activeliquid, either alone or in combination with other components at the timethat the particle or capsule is formed. Such matrix particles can bemade using physical or chemical techniques including, but not limited tospray drying, freeze drying, spinning disc, co-extrusion, spray chillingor spray cooling, liposome entrapment, inclusion complexation,centrifugal extrusion, and rotational suspension separation.

The spray-drying process typically uses a two-nozzle (internal orexternal mix) assembly, allowing air from an annular geometry to atomizeand implode the issuing liquid stream to form fine particles carryingthe coated product in a dispersed state. With high particle-specificsurface areas, heat from the drying chamber flash-evaporates the solventor aqueous media, rendering powder capsules that are cyclone-collectedinto a holding chamber. Some spray-drying operations use rotaryatomizers that spin at up to 50,000 rpm.

The freeze-drying process refers to the rapid freezing of a material atlow temperature followed by rapid dehydration by sublimation in a highvacuum. This method is used to preserve biological specimens or toconcentrate macromolecules with little or no loss of activity. Thisprocess is also called “lyophilization”.

The spray chilling or spray cooling process involves mixing the materialto be coated with the carrier and atomizing by cooling or chilling airas opposed to heated air in spray drying. Spray chilling is usually usedfor ferrous sulfate, vitamin, mineral, or acidulent coating. Frozenliquids, heat-sensitive materials and those not soluble in the usualsolvents can be coated in this manner. These materials are then releasedas the wall material is melted. Applications of spray chilling includedry soup mixes, foods with high fat contents, and bakery products.

The spinning disc method, similar to the spray-drying process, uses anemulsion or suspension containing the material to be coated, preparedwith a solution or melt of the coating material. The emulsion orsuspension is fed to the disc surface and forms a thin wetted layerthat, as the disc rotates, breaks up into airborne droplets from surfacetension forces that induce thermodynamic instabilities. Resultingcapsules are typically spherical. Because the emulsion or suspension isnot extruded through orifices, this technique permits use of a higherviscosity shell material and allows higher loading of the material inthe shell. The process also offers a broad range of particle sizes withcontrolled distribution.

Coextrusion coating methods can create fibers containing the activeingredient within fluid, high-viscosity, glassy sugars andcarbohydrates. These fibers can be chopped to create microcylinders.When the viscosity is low and the surface tension of the fluid is high,these extrudates would thermodynamically break up into tiny droplets,creating microcapsules.

The typical extrusion systems use stationary nozzle coextrusion,centrifugal coextrusion, or submerged nozzle coextrusion. All theseprocesses involve concentric nozzles, which pump the core materialthrough the inner nozzle while the shell (coating material) formulationis pumped through the annulus, allowing true “core-shell” morphologies.As the liquid stream exits the nozzle, local disturbances, such asinduced vibration or gravitational, centrifugal or drag force, controlparticle size. Typical capsules produced by coextrusion range from 100micrometers to 6 mm, or about the size of a human egg to the size of apencil eraser.

Fluidized bed coating involves suspending solid particles in atemperature and humidity controlled chamber of upwardly moving air orother fluidizing gas where the coating material is atomized. The amountof material that coats the particles is dependent on the length of timethat the particles are in the chamber.

Liposomes have been used as delivery and carrier systems by coatingvarious compounds in the aqueous layer of the liposome. Phospholipidsmake up the outer layer or layers of liposomes. The hydrophilic portionof the lipids is oriented towards the aqueous phase and the hydrophobicgroups associate with the hydrophobic ones of other lipid molecules.Folding of the lipid sheet into a spherical shape forms a very stablecapsule due to there being no interaction of the hydrophobic regions ofthe lipids with water. Aqueous or lipid-soluble materials, but not both,are entrapped in these membranes. Liposomes can range from a fewnanometers to a micron. Liposomes are made by three differentprocedures. The lipid formulation is mixed with a solvent system such as2:1 chloroform:methanol. The volume of solvent is decreased and the filmof lipids/solvent is then redispersed in an aqueous phase. This stepforms the liposomes and it can be performed in different ways includingphysical, two-phase, and detergent solubilization. The liposomes arethen recovered from the water.

Coacervation involves forming microcapsular shells by ionic interactionbetween two ionic polymers, typically a polyanion (such as acacia gum)and a polycation (such as gelatin). The concept of gelation as a coatingmethod involves using a technique such as cooling, crosslinking, or achemical reaction to form gelled microspheres or microcapsules. Forexample, reacting sodium alginate with calcium chloride forms theinsoluble calcium alginate.

Inclusion complexation involves the use of a material such asβ-cyclodextrin, in which the center is hydrophobic while the outersurface is hydrophilic due to its seven glucose units linked in a β-1,4configuration. In the center of the cyclodextrin, water molecules arereplaced by less polar molecules. The complex then precipitates out ofsolution. In the case of β-cyclodextrin, only water can serve as thesuspension medium. The precipitate is recovered and dried byconventional means.

Rotational or centrifugal suspension separation involves mixing the coreand wall materials and then adding to a rotating disc. The corematerials then leave the disc with a coating of residual liquid. Thecapsules are then dried or chilled after removal from the disc. Thewhole process can take between a few seconds to minutes.

The term “coating” as used herein refers to adherence, adsorption,loading and/or incorporation, to some extent, of at least one liquidcoating material onto and/or into a PUFA matrix or carrier particle orliquid pharmaceutical-containing matrix or carrier particle. Thiscoating liquid may remain in the liquid state, or be chilled to solidifyor evaporated to leave its solute as a solid coating residue. Thecoating material on the pharmaceutical or PUFA particle may be of anythickness; it need not necessarily be uniform on the surface of theparticle, nor is the entire surface of the particle necessarily covered.As used herein, the term coating includes the concept of encapsulation,but does not necessarily imply that the coated particle has beenencapsulated. The term “dry coating” as used herein refers to an aspectof the coating process wherein the particle to be coated is coated inits dry form, the process does not require dispersing the particles in acontinuous liquid phase prior to coating, and at the conclusion of theprocess the particle has no substantial gain in moisture level relativeto its uncoated form. The terms “coating” and “dry coating” are usedinterchangeably herein. As used herein, the term coating does notnecessarily imply that the coated particle has been protected fromoxidation or diffusion of volatile materials through the coating.

The term “size” as used herein refers to the longest diameter or longestaxis of the particle being coated. Throughout the disclosure, the letter“d” or “D” denotes diameter of the particle.

The term “moisture level” as used herein refers to the amount ofmoisture, for example water or solvent, that is present in the particlesbefore or after coating.

The term “oxidation” as used herein refers to the process wherein theatoms in an element lose electrons thereby making it moreelectropositive. The valence of the element is correspondingly increasedresulting in destruction of fat soluble vitamins, loss of naturalcolors, decrease or change in aroma and flavor, and creation of toxicmetabolites.

The term “volatile” as used herein refers to a compound or material thatis readily vaporizable at a relatively low temperature, i.e., itevaporates rapidly. “Volatiles” may refer, for example, to the aromavolatiles within foods, to volatiles in the environment that may diffuseinto foods and cause an “off” taste or smell, or to water moisture ingaseous form.

This invention can be practiced using any number of liquid coatingmaterials, general examples of which comprise a starch, gelatin, anatural color, a synthetic color, a sugar, a cellulose, a biodegradablepolymer, a biodegradable oligomer, an emulsifying wax, a fat, a wax, aphospholipid, a shellac, a flavoring agent, a moisture barrier, ataste-masking agent, an odor-masking agent, a shelf-life extendingagent, a lipid, a protein, cellulose derivatives, alginate, chitosan,surfactants or other wetting agents, carbohydrates, natural or syntheticpolymers, or a mineral. Thus, the term “liquid coating material” as usedherein includes, but is not limited to, materials that exist as liquidsat room temperature as well as those that are solids at roomtemperature, but have been formulated or dissolved into a liquid state,through the use of solvents or other formulating ingredients, during thecoating process. Many liquid coating materials can be used in theprocess of the invention. In the context of the invention, the term“liquid” refers to the physical state of the coating material as it isapplied to the particle. The finally-coated particle, when the particleis at the temperature and other conditions for delivery, may comprise acoating material in either a solid or liquid state. Coating materialsinclude a starch, gelatin, a natural food color, a synthetic food color,a sugar, a cellulose, a biodegradable polymer, a biodegradable oligomer,an emulsifying wax, a shellac, a flavoring agent, a moisture barrier, ataste-masking agent, an odor-masking agent, hydrophobicity orhydrophilicity agents, a shelf-life extending agent, a lipid, a protein,or a mineral. Specific coating ingredients can include, for example,ethyl cellulose, methyl cellulose, hydroxypropylcellulose,polyvinylpyrolidone, polyethylene, Aquateric, Eudragit™ (including anycommercial grade or formulations), acrylic coatings, Surelease™, bubblegum flavor, cherry flavor, grape flavor, sodium lauryl sulfate, sodiumdocusate, poly lactic acid, poly lactide glycolic acid, celluloseacetate pthalate. Further, the following materials comprise suitablecoating materials for certain applications, including as diluents:lactose, microcrystalline cellose, mannitol, dicalcium phosphate,starch, dextrates, sucrose; and as disintegrants: croscarmellose sodium,sodium starch glycolate, starch; and as binders: hydroxypropylcellulose, hydroxypyroylmethylcellulose, povidone, methyl cellulose; andas glidants/lubricants: silicon dioxide, stearic acid, a hydrocolloid, amonosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, asurface modifying agent, a sugar alcohol, a poly-ol, a flow aid, aninterparticle force control agent, magnesium stearate, talc, sodiumstearyl fumarate; and as surfactants: Tween 80; polysorbate,polyethylene glycol 400, Poloxamer®, glycol 3350, sodium lauryl sulfate(SLS), lecithin, oleic acid, polyoxyethylene alkyl ethers, Cremophor EL,Cremophor RH, polyoxyethlene stearates, sorbitan fatty acid ester; andas additional coating ingredients in the coating material, for example;hydroxypropyl cellulose, hydroxypropylmethylcellulose, titanium dioxide,colors, polyethylene glycols, triethyl citrate, triacetin, dibutylsebacate and polymethacrylates.

The coating material can specifically be a dispersion of one or morecompounds. For example, a coating dispersion may contain a polymer suchas ethylcellulose and a plasticizer such as triethyl citrate dissolvedin a suitable solvent and talc added as an antitackifier. Solvents thatcan be used in the process include water, acetone, ethanol, methanol,ethyl acetate, isopropyl alcohol, methyl acetate, n-propanol, ketones,toluene and methylene chloride, for example. A dispersion is definedherein as a two-phase system of which one phase consists of finelydivided particles (often in the colloidal size range) distributedthroughout a bulk substance, the particles being the disperse orinternal phase and the bulk substance the continuous or external phase.Under natural conditions the distribution is seldom uniform, but undercontrolled conditions the uniformity can be increased by addition ofwetting or dispersing agents (surfactants) such as a fatty acid.Examples of dispersions include liquid/liquid (emulsion) andsolid/liquid (paint).

PUFA-containing carrier particles or PUFA matrix particles, or liquidpharmaceutical-containing carrier particles or a liquid pharmaceuticalmatrix particles, can be coated with a combination of liquid coatingmaterials to enhance oxidative stability, protect efficacy and increaseshelf life. In addition, unique combinations of flavors, surfacemodifiers, colors, aromas, etc. can be coated onto the particles.Multiple coatings thus applied can lead to uniquely tailored carrierparticle or matrix particle with desired colors, flavorings andfreshness aspects; each coating having the ability to retain itsoriginal integrity and function, in that there is minimal “mixing” ofsubsequent layers which are applied to the particles. Another advantageis that the moisture level of the coated materials is substantially thesame as the moisture level of the uncoated materials.

Additionally, such particles can be further coated multiple times withthe same liquid coating material which is the same or different from thesubsequent liquid coating materials, enabling the claimed process toyield particles having particularly controlled thickness of the coatingmaterial. Such particles that are coated multiple times with the sameliquid coating material can be coated in a successive, batchwiseprocess. It is also possible to provide multiple coatings to a particleby delivering the output of a first apparatus to the feed of a secondapparatus in a successive, batchwise process.

There are several benefits of the instant process. It is believed thatthe process of the instant invention is more cost efficient thancurrently conducted coating processes, which commonly depend upon spraydrying techniques. Further, in one particularly important aspect, theinstant process has the flexibility to be operated as a successive,batchwise process. Further, overall particle quality appears to beimproved since this is a dry coating process, wherein the liquid coatingand drying step occur during the same pass of the food particle throughthe apparatus of the invention. Overall particle quality is alsoimproved in that the particles that have been coated with the instantprocess have been observed to retain their morphology, structuralintegrity and particle size throughout the process. And importantly, thestarting moisture level of the coated particles is substantiallyunchanged during the process. It is desirable that the process yieldsfinal coated particles that have not lost moisture and appear too dry,or have taken on additional moisture and become damp, soggy oragglomerated.

The flexibility which is inherent in the operation of the apparatus andprocess of the invention can result in production of high quality coatedPUFA-containing particles or PUFA matrix particles, and high qualityliquid pharmaceutical-containing particles or liquid pharmaceuticalmatrix particles having carefully-controlled and unique characteristics.For example, concentration values of the coating liquid, flow rates ofthe solid particle feed and the liquid coating feed, ratios of liquidfeeds to solid feeds, and temperature and velocity of the gas streamscan all be easily varied to yield such coated particles with particulardesired characteristics.

The size of the coated carrier particle or matrix particle should notexceed 20.0 mm. The lower limit on size will depend on the PUFA orpharmaceutical liquid being coated, intended use of the product, storageconditions, type of liquid coating material, etc.

The carrier particle when food use is intended for the coated particlecan be selected from the group consisting of a protein, fumed silica,titanium dioxide and calcium carbonate, a carbohydrate, a food particle,minerals, salts, antioxidants and lipids. Examples of carrier particlesalso include, but are not limited to, lactose, modified lactose, cornsyrup solids, maltodextrin, starch granules, cellulose and cellulosederivatives, soy cotyledon fiber, spray-dried or freeze dried foodparticles such as milk powder, instant beverage powders, infant formulapowders, creamers, etc.

Examples of suitable food particles which can be used to practice theprocess of the invention include, but are not limited to, a spray-driedfood particle, a freeze-dried food particle, a cereal food, a snackfood, a baked good, an extruded food, a fried food, a health food, adairy food, a pet food or animal feed.

Suitable liquid coating materials will be those which can be used safelyin any food or pharmaceutical application such as in any food,nutritional supplement, beverage, infant formula and the like.Applications intended for human consumption should generally utilizematerials that are generally recognized as safe (“GRAS”). If theintended application is for incorporation into a pet food or animalfeed, then other liquid coating or coating materials may be suitable.For example, some materials recognized as GRAS include but are notlimited to the following: polysaccharides/hydrocolloids such as starch,agar/agarose, pectin/polypectate, carrageenan and other gums; proteinssuch as gelatin, casein, zein, soy and albumin; fats and fatty acidssuch as mono-, di-, and triglycerides, lauric, capric, palmitic andstearic acid and their salts; cellulosic derivatives; hydrophilic andlipophilic waxes such as shellac, polyethylene glycol, carnauba wax orbeeswax; sugar derivatives, etc. Further examples of such liquid coatingmaterials include, but are not limited to, a sweetening agent, a foodflavoring agent or enhancer, a food color, a food aroma agent, ananti-caking agent, an humectant, an antimicrobial agent, an antioxidant,a surface modifying agent, a carbohydrate, a protein, a lipid, amineral, a nutritional supplementing agent, a pharmaceutical, ormixtures thereof.

Non-limiting further examples of coating materials include starch,gelatin, natural food color, a synthetic food color, a sugar, acellulose, a biodegradable polymer, a biodegradable oligomer, anemulsifying wax, a shellac, a flavoring agent, a moisture barrier, ataste-masking agent, an odor-masking agent, hydrophobicity orhydrophilicity agents, a shelf-life extending agent, a lipid, a protein,or a mineral. Specific coating ingredients can include, for example,ethyl cellulose, methyl cellulose, hydroxypropylcellulose,polyvinylpyrolidone, polyethylene, Aquateric, Eudragit™ (including anycommercial grade or formulations), acrylic coatings, Surelease™, bubblegum flavor, cherry flavor, grape flavor, sodium lauryl sulfate, sodiumdocusate, poly lactic acid, poly lactide glycolic acid, celluloseacetate pthalate. Further, the following materials comprise suitablecoating materials for certain applications, including as diluents:lactose, microcrystalline cellose, mannitol, dicalcium phosphate,starch, dextrates, sucrose; and as disintegrants: croscarmellose sodium,sodium starch glycolate, starch; and as binders: hydroxypropylcellulose, hydroxypyroylmethylcellulose, povidone, methyl cellulose; andas glidants/lubricants: silicon dioxide, stearic acid, a hydrocolloid, amonosaccharide, a disaccharide, an oligosaccharide, a polysaccharide, asurface modifying agent, a sugar alcohol, a poly-ol, a flow aid, aninterparticle force control agent, magnesium stearate, talc, sodiumstearyl fumarate; and as surfactants: sodium lauryl sulfate, Tween 80;Poloxamer®; and as coating ingredients: hydroxypropyl cellulose,hydroxypropylmethylcellulose, titanium dioxide, colors, polyethyleneglycols, triethyl citrate, triacetin, dibutyl sebacate andpolymethacrylates.

Examples of sweetening agents include, but are not limited to, sugarsubstitutes such as saccharin, cyclamate, monellin, thaumatins,curculin, miraculin, stevioside, phyllodulcin, glycyrrhizin,nitroanilines, dihydrochalcones, dulcin, suosan, guanidines, oximes,oxathiazinone dioxides, aspartame, alitame, and the like. There can alsobe mentioned monosaccharides and oligosaccharides. Examples ofmonosaccharides include, but are not limited to, galactose, fructose,glucose, sorbose, gatose, tagatose and xylose. As oligosaccharides therecan be entioned, sucrose, lactose, lactulose, maltose, isomaltose,maltulose, accharose and trehalose. Other sweetening agents that canalso be used include, but are not limited to, high fructose corn syrup.Sugar alcohols, including but not limited to sorbitol, manitol, xylitol,erythritol and the like can also be used.

Examples of food flavoring agents or enhancers include, but are notlimited to, monosodium glutamate, maltol, 5′-mononucleotides, such asinosine, and the like.

Examples of food colors include, but are not limited to, tartrazine,riboflavin, curcumin, zeaxanthin, β-carotene, bixin, lycopene,canthaxanthin, astaxanthin, β-apo-8′-carotenal, carmoisine, amaranth,Ponceau 4R (E124), Carmine (E120), anthocyanidin, erythrosine, Red 2G,Indigo Carmine (E132), Patent Blue V (E131), Brilliant blue,chlorophyll, chlorophyllin copper complex, Green S (E142), Black BN(E151), and the like.

Examples of food aroma agents include, but are not limited to, carbonylcompounds, pyranones, furanones, thiols, thioethers, di- andtrisulfides, thiophenes, thiazoles, pyrroles, pyridines, pyrazines,phenols, alcohols, hydrocarbons, esters, lactones, terpenes, volatilesulfur compounds and the like.

Examples of an anti-caking agents include, but are not limited to,sodium, potassium, calcium hexacyanoferrate (II), calcium silicate,magnesium silicate, tricalcium phosphate, magnesium carbonate and thelike.

Examples of humectants include, but are not limited to, 1,2-propanediol,glycerol, manitol, sorbitol and the like.

Examples of antimicrobial agents include, but are not limited to,benzoic acid, PHB esters, sorbic acid, propionic acid, acetic acid,sodium sulfate and sodium metabisulfite, diethyl pyrocarbonate, ethyleneoxide, propylene oxide, nitrite, nitrate, antibiotics, diphenyl,o-phenylphenol, thiabendazole and the like.

Examples of antioxidant agents include, but are not limited to,tocopherols, 2,6-di-tert-butyl-p-cresol (BHT),tert-butyl-4-hydroxyanisole (BHA), propylgallate, octylgallate,dodecylgallate, ethoxyquin, ascorbyl palmitate, ascorbic acid and thelike.

Examples of surface modifying agents include, but are not limited to,mono-, diaglycerides and derivatives, sugar esters, sorbitan fatty acidesters, polyoxyethylene sorbitan esters, stearyl-2-lactylate and thelike.

Examples of nutritional supplementing agents include, but are notlimited to, vitamins group consisting of fat soluble vitamins groupconsisting of retinol (vit A), calciferol (vit D), tocopherol (vit E),phytomenadione (vit K1), water soluble vitamins group consisting ofthiamine (vit B1), riboflavin (vit B2), pyridoxine (vit B6),nicotinamide (niacin), pantothenic acid, biotin, folic acid,cyanocobalamin (vit B12), ascorbic acid (vit C), polyunsaturated fattyacids (PUFA), and the like.

Other carbohydrates which can be used in a liquid coating materialinclude polysaccharides such as agar, alginates, carrageenans,furcellaran, gum arabic, gum ghatti, gum tragacanth, karaya gum, guarangum, locust bean gum, tamarind flour, arabinogalactan, pectin, starch,modified starches, dextrins, cellulose, cellulose derivatives,hemicelluloses, xanthan gum, scleroglucan, dextran, polyvinylpyrrolidone and the like.

Examples of lipids include, but are not limited to, saturated andunsaturated fatty acids, mono- and diacylglycerols triacylglycerols,phospholipids, glycolipids, phosphatidyl derivatives,glycerolglycolipids, sphingolipids, lipoproteins, diol lipids, waxes,cutin and the like.

Examples of minerals include, but are not limited to, salts of sodium,potassium, magnesium, calcium, chloride, phosphate, iron, copper, zinc,manganese, cobalt, vanadium, chromium, selenium, molybdenum, nickel,boron, silica, silicon, fluorine, iodine, arsenic and the like.

Any of the liquid coating materials discussed herein can be used inpracticing the process of the invention. In addition, there can be useda shelf-life extending agent such as an oxygen barrier and a flavorretaining agent such as a volatile barrier.

Any PUFA can be used to practice the invention. There can be mentionedγ-linolenic acid (GLA), dihomo-γ-linolenic acid, arachidonic acid (ARA),docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA).

Examples of foods into which an coated PUFA-containing carrier particleor coated PUFA matrix particle, or pharmaceutical-containing carrierparticle or pharmaceutical matrix particle can be incorporated include,but are not limited to, a cereal food product, a snack food product, abaked good product, a fried food product, a health food product, infantformula, beverages, a dairy product, a nutritional supplement, a petfood product, and animal feed.

A cereal food product is a food product derived from the processing of acereal grain. A cereal grain includes any plant from the grass familythat yields an edible grain (seed). The most popular grains are barley,corn, millet, oats, quinoa, rice, rye, sorghum, triticale, wheat andwild rice. Examples of a cereal food product include, but are notlimited to, whole grain, crushed grain, grits, flour, bran, germ,breakfast cereals, extruded foods, pastas, and the like.

A baked good product comprises any of the cereal food products mentionedabove and has been baked or processed in a manner comparable to baking,i.e., to dry or harden by subjecting to heat. Examples of a baked goodproduct include, but are not limited to breadcrumbs, baked snacks,mini-biscuits, mini-crackers, mini-cookies, and mini-pretzels.

A snack food product comprises any of the above or below described foodproducts.

A fried food product comprises any of the above or below described foodproducts that has been fried.

A health food product is any food product that imparts a health benefit.Many oilseed-derived food products may be considered as health foods.There can be mentioned soybeans, flax seed, sesame seed, pumpkin seeds,sunflower seeds, or food products processed from these seeds or whichare incorporated into foods. For example, soy nuggets and soy nuts canbe mentioned. In addition to oilseed-derived food products,fruit-derived food products can be mentioned such as fruit bits, driedberries, and the like.

A beverage is any drinkable liquid. For example, there can be mentionednon-carbonated drinks; carbonated drinks; fruit juices, fresh, frozen,canned or concentrate; still or sparkling water; flavored or plain milkdrinks, etc. Adult and infant nutritional formulas are well known in theart and commercially available (e.g., Similac®, Ensure®, Jevity®, andAlimentum® from Ross Products Division, Abbott Laboratories).

A dairy product is a product derived from milk. These products include,but are not limited to, whole milk, skim milk, fermented milk productssuch as yogurt or sour milk, cream, butter, condensed milk, dehydratedmilk, coffee whitener, ice cream, cheese, whey products, and lactose.

Infant formulas are liquids or reconstituted powders fed to infants andyoung children. They serve as substitutes for human milk. Infantformulas have a special role to play in the diets of infants becausethey are often the only source of nutrients for infants. Althoughbreast-feeding is considered the best nourishment for infants, infantformula is a close enough second that babies not only survive but alsothrive. Infant formula compositions are becoming increasingly close tothe composition of breast milk.

A pet food product is a product intended to be fed to a pet such as adog, cat, bird, reptile, fish, rodent and the like. These products caninclude the cereal and health food products above, as well as meat andmeat byproducts, grass and hay products, including but not limited toalfalfa, timothy, oat or brome grass and the like.

Animal feed is a product intended to be fed to animals such as turkeys,chickens, cattle and swine and the like. As with the pet foods above,these products can include cereal and health food products, meat andmeat byproducts, and grass and hay products as listed above.

The apparatus used to practice the process of this invention isgenerally as described in commonly-owned PCT application WO 97/07879which is discussed above. An apparatus according to the presentinvention is shown generally at 10 in FIG. 1.

The apparatus of the present invention comprises a first chamber, shownat 12 in FIGS. 1 and 2. A flow restrictor 14 is disposed at one end ofthe first chamber. The flow restrictor is typically disposed at thedownstream end of the first chamber, as shown in FIGS. 1 and 2. Flowrestrictor 14 has an outlet end 14 a, as shown in the detailed view ofFIG. 2.

Although the flow restrictor is shown as a different element from thefirst chamber, it may be formed integrally therewith, if desired. Theflow restrictor of the present invention may have variousconfigurations, as long as it serves to restrict flow and therebyincrease the pressure of the fluid passing through it. Typically, theflow restrictor of the present invention is a nozzle.

A first, or liquid, inlet line 16 as shown in FIGS. 1 and 2 is disposedin fluid communication with the first chamber for metering a liquidcomposition into the chamber. Liquid inlet line 16 meters the liquidcomposition into first chamber 12 through the outlet of flow restrictor14, and preferably in the center of the flow restrictor when viewedalong the axial length thereof. The liquid composition is meteredthrough liquid inlet line 16 by a metering pump 18 from a storagecontainer 20 containing the liquid composition as shown in FIG. 1.

The liquid coating composition may be wherein a material which is usedas the coating material is dissolved in a liquid, or a slurry, adispersion, or an emulsion where a material which is used as the coatingmaterial is undissolved in a liquid. Alternatively, the liquid coatingcomposition may be a melt, which is used as the coating material. Bymelt is meant any substance at a temperature at or above it meltingpoint, but below its boiling point. In any of these cases, the liquidcomposition may include components other than the coating material. Itshould be noted that when the liquid composition is a melt, storagecontainer 20 must be heated to a temperature above the melt temperatureof the liquid composition in order to maintain the liquid composition inmelt form. Further, the coating material can be a dispersion of one ormore compounds. For example, a coating dispersion may contain a polymersuch as ethylcellulose and a plasticizer such as triethyl citratedissolved in a suitable solvent and talc added as an antitackifier.Solvents that can be used in the process include water, acetone,ethanol, methanol, ethyl acetate, isopropyl alcohol, methyl acetate,n-propanol, ketones, toluene and methylene chloride, for example. Adispersion is defined herein as a two-phase system of which one phaseconsists of finely divided particles (often in the colloidal size range)distributed throughout a bulk substance, the particles being thedisperse or internal phase and the bulk substance the continuous orexternal phase. Under natural conditions the distribution is seldomuniform, but under controlled conditions the uniformity can be increasedby addition of wetting or dispersing agents (surfactants) such as afatty acid. Examples of dispersions include liquid/liquid (emulsion) andsolid/liquid (paint).

The apparatus for coating a PUFA carrier or matrix particle or a liquidpharmaceutical matrix or carrier particle further includes a second, orgas, inlet line 22 disposed in fluid communication with the firstchamber as shown in FIGS. 1 and 2. Generally, the gas inlet line shouldbe disposed in fluid communication with the first chamber upstream ofthe flow restrictor. Gas inlet line 22 injects a first gas streamthrough the flow restrictor to create turbulent flow of the gas stream.The turbulence subjects the liquid composition to shear forces thatatomize the liquid composition.

The first gas stream should have a stagnation pressure sufficient toaccelerate the gas to at least one-half the velocity of sound, orgreater, prior to entering the flow restrictor to ensure that aturbulent flow of gas of sufficient intensity will be formed at theoutlet of the flow restrictor. The velocity of sound for a particulargas stream, e.g., air or nitrogen, will be dependent on the temperatureof the gas stream. This is expressed by the equation for the speed ofsound, C:C=√{square root over (kgRT)}

-   -   where:        -   k=ratio of specific heats for the gas        -   g=acceleration of gravity        -   R=universal gas constant        -   T=absolute temperature of the gas

Thus, the acceleration of the first gas stream is dependent on thetemperature of the gas stream.

As noted above, it is the pressurized gas that causes the atomization ofthe liquid composition. The pressure of the liquid composition in theliquid inlet line just needs to be enough to overcome the systempressure of the gas stream. It is preferable that the liquid inlet linehas an extended axial length upstream of the flow restrictor 14. If theliquid inlet line is too short, the flow restrictor becomes plugged.

The apparatus of the present invention also comprises means disposed inthe second inlet line and upstream of the flow restrictor for optionallyheating the first gas stream prior to injection through the flowrestrictor. Preferably, the heating means comprises a heater 24 as shownin FIG. 1. Alternatively, the heating means may comprise a heatexchanger, a resistance heater, an electric heater, or any type ofheating device. Heater 24 is disposed in second inlet line 22. A pump 26as shown in FIG. 1 conveys the first gas stream through heater 24 andinto first chamber 12. When a melt is used as the coating material, thegas stream should be heated to a temperature around the melt temperatureof the liquid composition to ensure solidification of the melt on theparticles. As also noted above for the apparatus, when using a melt, itis also helpful if auxiliary heat is provided to the first inlet line,which supplies the melt prior to injection, to prevent pluggage of theline.

The apparatus of the present invention further includes a second chamber32 surrounding the first chamber as shown in FIGS. 1 and 2. The secondchamber encloses the turbulent flow of gas. The apparatus of the presentinvention further includes a hopper 28 as shown in FIGS. 1 and 2. Hopper28 introduces a particle into the region of the second chamber 32 inwhich turbulent flow of the gas has been created. It is preferable thatthe outlet end of the flow restrictor is positioned in the first chamberbeneath the hopper at the centerline of the hopper (i.e., the region inwhich the turbulent flow of gas is created). This ensures that theparticles are introduced directly into the turbulent flow of gas. Thisis important because, as noted above, the turbulence subjects the liquidcomposition to shear forces that atomize the liquid composition. It alsoincreases operability by providing a configuration for feeding theparticles most easily. In addition, the shear forces disperse and mixthe atomized liquid composition with the particles, which allows theparticles to be coated within the turbulent flow. Hopper 28 may be feddirectly from a storage container 30 as shown by arrow 29 in FIG. 1. Thehopper of the present invention may include a metering device foraccurately metering the particles at a particular ratio to the liquidfeed from liquid inlet line 16 into the zone of turbulence. Thismetering establishes the level of coating on the particle or coating ofthe particle. Typically, the hopper of the present invention is open tothe atmosphere. When a melt is used, it is preferred that the particlesare at ambient temperature because this facilitates solidification ofthe melt after the melt which is initially at a higher temperature,encapsulates/coats the particle in the zone of turbulent flow.

The apparatus of the present invention further includes an inlet 34 forintroducing a second gas stream into the second chamber. The inlet ofthe second gas stream is preferably positioned at or near the upstreamend of second chamber 32. The outlet of second chamber 32 is connectedto a collection container, such as that shown at 36 in FIG. 1. Thesecond gas stream acts to reduce any tendency for recirculation withinthe region of turbulent flow and cools and conveys the coated particlestoward the collection container as illustrated by arrow 31 in FIG. 2.

In particular, when a solution, dispersion or slurry is used, the solidof the solution, dispersion or slurry cools between the zone ofturbulence and container so that by the time the particle reaches thecontainer, a solid coating comprising the solid of the solution,dispersion or slurry is formed on the particle. When a melt is used, theliquid composition cools within the zone of turbulence so that by thetime the particle reaches the container, a solid coating comprising themelt is formed on the particle. The first gas stream, as well as thesecond gas stream, is vented through the top of collection container 36.

For the configuration as shown in FIGS. 1 and 2, inlet 34 may beconnected to a blower, not shown, which supplies the second gas streamto the second chamber. However, the blower and second chamber 32 may beeliminated, and the first gas stream may be used to cool the particlesand to convey them to container 36. In this case, the solid from thesolution, dispersion or slurry or the melt cools and solidifies on theparticle in the atmosphere between the zone of turbulence and thecollection container, and the coated particles fall into collectioncontainer 36.

It is preferable that the axial length of the region of the secondchamber in which the turbulent flow is created is about ten times thediameter of the second chamber. This allows the pressure at the outletof the flow restrictor to be at a minimum. Particles are fed into secondchamber 32 as shown in FIGS. 1 and 2 near the outlet of the flowrestrictor, which is preferably positioned at the centerline of thehopper. If the pressure at the outlet is too great, the particles willback flow into the hopper.

The pressure of the second gas stream must be sufficient to assist inconveying the coated particles from the zone of turbulence to thecollection zone, but should be at lower than the pressure of the firstgas stream. This is because a high relative velocity difference betweenthe first gas stream and the second gas stream is needed to produce asufficient degree of turbulence to encapsulate/coat the particles.

It should be noted that the process of the present invention may bepracticed using the apparatus illustrated in FIGS. 1, 2 and 3, althoughit should be understood that the process of the present invention is notlimited to the illustrated apparatus. Moreover, it should be noted thatwhile one pass, or cycle, of the process of the present inventionsubstantially or completely encapsulate/coats the particle, more thanone pass may be used to adhere additional coating material to theparticle, depending on the desired thickness of the liquid coatingmaterial.

The process comprises the steps of metering a liquid composition into aflow restrictor, such as flow restrictor 14 as shown in FIGS. 1 and 2.As described above for the apparatus, the liquid composition may be asolution, dispersion, slurry, emulsion or melt.

The process of the present invention further comprises injecting a gasstream, for instance from a gas inlet line such as that shown at 22 inFIGS. 1 and 2, through the flow restrictor concurrently with meteringthe liquid composition into the flow restrictor, to create turbulentflow of gas at the outlet of the flow restrictor. The shear in the zoneof turbulence atomizes the liquid composition.

The gas stream is controlled prior to injecting it through the flowrestrictor. The gas stream may be heated by a heater, such as heater 24as shown in FIG. 1. As noted above for the apparatus, when the liquidcomposition is a solution, dispersion or slurry, the gas stream isheated to a temperature sufficient to vaporize the liquid of thesolution, dispersion or slurry and to leave the solid of the solution,dispersion or slurry remaining. When the liquid composition is a melt,the gas stream should be heated to a temperature around the melttemperature of the liquid composition, to keep the liquid composition,and in particular, the melt, in liquid (i.e., melt) form. As also notedabove for the apparatus, when using a melt, it is also helpful ifauxiliary heat is provided to the first inlet line which supplies themelt prior to injection, to prevent pluggage of the line.

The process of the present invention also comprises the step of adding aPUFA carrier or matrix particle or liquid pharmaceutical carrier ormatrix particle to the zone of turbulence concurrently with the meteringof the liquid composition and the injection of the gas stream. Thismixes the particle with the atomized liquid composition at the zone ofturbulence. This mixing at the zone of turbulence coats the particlewith the liquid coating material. The particle is preferably metered inorder to control the ratio of the particle and the liquid added at thezone of turbulence. This establishes the level of coating of theparticle. When a solution, dispersion or slurry is used, the heat fromthe heated gas stream serves to evaporate the liquid of the solution,dispersion or slurry, leaving the solid of the solution, dispersion orslurry remaining to encapsulate/coat the particle. The mixing at thezone of turbulence then coats the particle with the remaining solid fromthe solution, dispersion or slurry. When a melt is used, the mixing atthe zone of turbulence coats the particle with the melt. Particle sizesshould not exceed 20.0 mm.

As noted above, the zone of turbulence is formed by the action ofinjecting the gas at high pressure through the flow restrictor. Asdiscussed above with respect to the apparatus, it is preferable that thegas stream is accelerated to at least about one-half the velocity ofsound prior to injection to ensure that a zone of turbulence ofsufficient intensity will be formed at the outlet of the flowrestrictor.

The residence time of the particles in the zone of turbulence isdetermined by the geometry of the first chamber and the amount of gasinjected from the gas inlet line. The average residence time of theparticle within the zone of turbulence is preferably less than 250milliseconds. More preferably, the average residence time of theparticle within the zone of turbulence is in the range of 25 to 250milliseconds. Short residence times can be achieved because of theaction of the zone of turbulence. The short residence times make theprocess of the present invention advantageous compared to conventionalcoating processes because the time, and hence, the cost of coatingparticles, are reduced. Typically, the particles are fed from a hopper,such as hopper 28 as shown in FIGS. 1 and 2, which is open to theatmosphere. As noted above for the apparatus, when the liquidcomposition is a melt, it is preferred that the particles be at ambienttemperature because this will facilitate solidification of the meltafter the melt (which is initially at a higher temperature) coats theparticle in the zone of turbulence.

The process of the present invention may further comprise the step ofadding another gas stream upstream of the zone of turbulence for coolingand conveying the coated particle. This other gas stream is addedthrough a chamber, such as second chamber 32 as shown in FIGS. 1 and 2.As explained above for the apparatus, the pressure of the second gasstream must be sufficient to assist in conveying the coated particlesfrom the zone of turbulence to the collection container, but should beat lower than the pressure of the first gas stream in order to achievecoating. When a solution, dispersion or slurry is used, the solid of thesolution, dispersion or slurry cools and solidifies on the particle inthe second chamber between the zone of turbulence and a collectioncontainer, such as collection zone 36 as described above. When a melt isused, the melt cools and solidifies on the particle in the secondchamber between the zone of turbulence and the collection container.When a second chamber is not included, the solid or the melt cools andsolidifies on the particle in the atmosphere between the zone ofturbulence and the collection container, and the coated particles fallinto the container.

The coating materials are generally liquid in nature, and can be singleor multiple chemical compositions. Thus, they may be pure liquids,dispersions including suspensions and emulsions, melted polymers,resins, and the like. These materials generally have viscosities in the1 to 2,000 centipoise range. Coatings that are applied can behydrophilic, hydrophobic or amphoteric in nature, depending on theirchemical composition. When more than one coating layer is applied, itcan be either as another shell adhering to the previous coating layer,or as individual particles on the surface of the material to be coated.These materials may also be reactive so that they cause the materialthey are coating to increase in viscosity or change to a solid orsemi-solid material. So that the coating formed on the selected materialis in the range stated above, the coating material should be capable ofbeing molecularly dispersed, so that the coating can grow from themolecular level.

The apparatus as shown in FIGS. 1, 2, and 3 can be used for a number ofprocesses. One such process is that of coating a PUFA-orpharmaceutical-containing particle or PUFA or pharmaceutical matrixparticle. In this process, the particle or matrix particle enters theapparatus and the material that will be used to coat the particles isfed into the apparatus through the hopper into the high shear/turbulencezone. The resulting atomized coating material coats the surface of theparticle, and it is pneumatically transported through the apparatus. Thetemperature of the process generally exceeds the boiling point of thesolvent (at least by 5° C. in many cases). This ensures rapidevaporation of the solvent from the liquid coated particles, wheredesired. The coated material is then transported out of the apparatus ina substantially dry state, such that there is substantially no netmoisture gain from one end of the process to the other. The moisturecontent is measured by a Cenco moisture balance operated at 105° C.Thus, the coating and drying of the material is accomplished in a singlestep. This is important so that the quality of the particle ismaintained, as the particles are uniformly coated, the material is notdegraded by excessive exposure to relatively high temperatures, and theparticles do not agglomerate or stick to the sides of the vessels.Furthermore, the moisture level of the coated particle is substantiallythe same as the moisture level of the uncoated particle.

A convective drying process is used for removing residual volatiles thatresult from putting a solution, dispersion, slurry or emulsion coatingonto the surface of a particle. The design of the process precludes wetparticles from reaching any wall to which they may stick, which improvesthe cleanliness of the system, and may also include a recycle systemwhich can reduce any interparticle or particle-to-wall sticking thatmight otherwise occur. This process may be selected from any number ofmethods, including but not limited to flash drying, pneumatic conveyordrying and spray drying, or combinations thereof. Residence times fordrying are generally less than a minute, and preferably in themillisecond time frame.

As shown in FIG. 3, the apparatus of FIGS. 1 and 2 can have an alternateconfiguration. Solids enter the apparatus through hopper 43. Liquid isadded via a liquid inlet tube 42 located at the top of the apparatus, sothat the liquid exits into the high shear/turbulence zone. Hot gasenters chamber 44 through nozzle 41. Product outlet from chamber 44exits to collector 40. This configuration can allow for faster changesof liquid used for coating, and is less expensive to maintain.

EXAMPLES

The invention is further described by the following Examples, which areprovided for illustration and are not to be construed as limiting thescope of the invention.

Coating layers that were produced according to the Examples werecalculated as their percent contribution to the mass of the coatedparticle. Coating levels were determined based on mass balance.

Example 1 Preparation of PUFA-Coated Isolated Soy Protein Particles

A preparation of isolated soy protein (“ISP”, Supro 500E, DuPont ProteinTechnologies, St. Louis, Mo.) was coated with polyunsaturated fatty acidin order to produce PUFA coated protein in a single coating and dryingprocess. The apparatus as shown in FIG. 1 had a mixing chamber 32 mm indiameter and 300 mm in length with a nozzle throat of 10 mm and acentral liquid feed tube of 6.5 mm O.D. and 4.8 mm I.D. The apparatushas a single screw metering feeder (AccuRate) or a vibrating feeder(Syntron) for metering the solid particles. A peristaltic pump was fitwith 6.5 mm Tygon elastomer tubing for metering the liquid. Supro 500Ewas used without further treatment and was metered to the system at 990grams/minute. PUFA-enriched oil (Omega Protein Inc., Houston, Tex.) wasat 22° C. and was metered at 21.9 g/min. to the center tube using theperistaltic metering pump. Nitrogen gas was supplied to the nozzle at414 KPa, and was at 22° C. at the nozzle. The nitrogen gas was used toatomize the PUFA-enriched oil, producing a negative pressure in themixing zone to induce the addition of the Supro 500E, and provide theheat for evaporating any residual moisture from the Supro 500E. Theproduct of the mixing/drying was collected in a polyester twill bagfilter immediately. The product had an oil-coating layer equal to 2.16%of the final mass of the coated particle. There was no gain in residualmoisture (as measured by a Cenco moisture balance) when compared to theparticles prior to coating. The PUFA oil-coated ISP material retainedthe dry flowable property of the uncoated ISP starting material.

Examples 2-7 Preparation of PUFA-Coated Isolated Soy Protein Particleswith Various Levels of PUFA Oil Coating

Additional lots of PUFA oil-coated isolated soy protein particles wereprepared using the apparatus and method of Example 1. Differing levelsof PUFA oil in the final product were achieved by modifying theoperating parameters of the process. The modifications to the processand the amount of PUFA oil in the products thus formed are listed inTable 1. Menhaden oil (OmegaPure, Houston, Tex.) was used as the PUFAoil in Example 7. TABLE 1 Drying Gas ISP PUFA PUFA oil PUFA oil gas,nozzle feed oil feed in finished Ex- pressure temp. rate feed rate temp.particle ample (Kpa) (° C.) (g/min) (g/min) (° C.) (%) 2 N₂, 414 18.51181 158 22 11.8 3 N₂, 414 16.2 736 80.3 22 9.8 4 N₂, 414 15.9 1004 18422 15.5 5 N₂, 414 15.5 604 235 22 28.1 6 N₂, 414 19.5 1006 92 22 8.4 7N₂, 414 19. 1104 138 22 11.1PUFA oil coating layers on the isolated soy protein particles rangedfrom approximately 2% to approximately 30% of the final product.

Example 8 PUFA Oil-Coated Isolated Soy Protein Particles Further Coatedwith a Layer of Sucrose

The PUFA oil-coated isolated soy protein prepared as described inExample 3, above, was used as the solid feed material in the coatingprocess of the invention to produce a PUFA oil-coated particle with arelatively light barrier layer of solid sucrose. The apparatus was asdescribed in Example 1 with the following operational modifications. Thenitrogen employed as drying gas had a nozzle temperature of 315° C. ThePUFA oil-coated isolated soy protein particles were metered into theapparatus at a rate of 743 g/min. A solution of food grade sucrose (84%w/w in water) was metered into the apparatus at a rate of 25 g/min andat a temperature of 95° C. The dry coated particles were collected asdescribed in Example 1. The resultant particle possessed a first,internal coating layer of PUFA oil and a second, externalcoating/coating layer of sucrose that constituted 2.8% of the finishedproduct. The solid coating/coating layer on a PUFA material is useful asa barrier against the undesirable effects of oxidation, and it improvesthe handling characteristics of the PUFA oil-coated particles.

Oxidation rates of the PUFA oil component of the particles may bedetermined by standard methods available in the art. These include theActive Oxygen Method, method Cd12-57 of the American Oil Chemists'Society (AOCS), and the Oil Stability Index, AOCS method Cd 12b-92.

Example 9 PUFA Oil-Coated Isolated Soy Protein Particles Further Coatedwith a Heavy Layer of Sucrose

The PUFA oil-coated isolated soy protein prepared as described inExample 3, above, was used as the solid feed material in thecoating-process of the invention to produce a PUFA oil-coated particlewith a heavy layer of solid sucrose. The apparatus was as described inExample 1 with the following operational modifications. The nitrogenemployed as drying gas had a nozzle temperature of 319° C. The PUFAoil-coated isolated soy protein particles were metered into theapparatus at a rate of 743 g/min. A solution food grade of sucrose (84%w/w in water) was metered into the apparatus at a rate of 53 g/min andat a temperature of 95° C. The dry coated particles were collected asdescribed in Example 1. The resultant particle possessed a first,internal coating of PUFA oil and a second, external coating of sucroseconstituting 8.1% of the finished product. The solid coating on a PUFAmaterial is useful as a barrier against the undesirable effects ofoxidation, and it improves the handling characteristics of the PUFAoil-coated particles.

Oxidation rates of the PUFA oil component of the particles may bedetermined by standard methods available in the art. These include theActive Oxygen Method, method Cd12-57 of the American Oil Chemists'Society (AOCS), and the Oil Stability Index, AOCS method Cd 12b-92.

Example 10 PUFA Oil-Coated Isolated Soy Protein Particles Further Coatedwith a Layer of Protein

The PUFA oil-coated isolated soy protein prepared in Example 7, above,was further coated with casein to provide a barrier to moisture andoxidation to the PUFA material. The apparatus and process was asdescribed in Example 1 with the following operational modifications. ThePUFA oil-coated isolated soy protein particles (12.5% PUFA oil coating)were metered into the apparatus at a rate of 300 g/min. A solution ofcasein (20% w/w in water, prepared from Non Fat Dry Milk Powder Low HeatA Grade, T. C. Jacoby & Co. Inc., St Louis, Mo.) was metered into theapparatus at a rate of 48 g/min and at a temperature of 30° C. The drycoated particles were collected as described in Example 1. The resultantparticle possessed a first, internal coating of PUFA oil and a second,external coating of dried casein that constituted 3.1% of the finishedproduct. Such a solid coating on a PUFA material is useful as a barrierto both moisture and oxidation.

Examples 11-14 PUFA Oil-Coated Isolated Soy Protein Particles FurtherCoated with a Various Levels of Protein

Additional lots of isolated soy protein particles coated with both PUFAoil and casein were prepared as generally described in Example 10. Allof the products of these Examples possessed a barrier layer of driedcasein to protect the PUFA oil that had first been coated onto theisolated soy protein. Differing amounts of casein in the final productwere achieved by modifying the operating parameters of the process. Themodifications to the process and the amount of casein in the productsthus formed are listed in Table 2. TABLE 2 Drying Gas Solid CaseinCasein Casein gas, nozzle feed oil feed in finished Ex- pressure temp.rate feed rate temp. particle ample (Kpa) (° C.) (g/min) (g/min) (° C.)(%) 11 N₂, 414 294 300 48 30 3.1 12 N₂, 414 285 300 48 30 6.1 13 N₂, 414276 300 47 30 9.0 14 N₂, 414 281 300 48 30 11.8

The casein barrier coating on the PUFA oil-coated isolated soy proteinranged from approximately 3% to 12% of the final product.

Example 15 Isolated Soy Protein Particle Multiply Coated with PUFA Oil,Casein, and a High Melting Temperature Fat

The multiply coated isolated soy protein particle produced in Example13, above, was further processed to provide an additional barrier layerof fat with a high melting temperature. The apparatus and process is asdescribed in Example 1, with the following modifications to the process.Isolated soy protein particles possessing coatings of PUFA oil andcasein were prepared as described in Example 13. The particles weremetered to the system at 611 g/min. A preparation of high meltingtemperature fat (Dritex, ACH Food Companies, Cordova, Tenn.) was meteredat 120 g/min. to the center tube at 80° C. using the peristalticmetering pump. Nitrogen gas was supplied to the nozzle at 414 KPa, andwas at 216° C. at the nozzle. The dry coated particles were collected asdescribed in Example 1. The resultant particle possessed a firstinternal coating of PUFA oil, a second internal coating casein, and athird, external coating of Dritex that constituted 16.4% of the finishedproduct.

The high melting fat layer provides additional protection againstmoisture. The effectiveness of the moisture barrier was demonstrated bydifferential, temperature-dependent dispersal of the protein into water.High melting point fat-coated particles (approximately 1 g) were placedinto 150 mL of water in a beaker at room temperature. A portion of thefat-coated particles floated on the surface of the water, while theremainder sank below the surface. The beaker was shaken gently andobserved for 5 minutes. No substantial change in the appearance of thewater was observed. It was concluded that the oil and soy protein in theparticles were protected from the water by the fat barrier because thewater did not become cloudy. Similarly, high melting point fat-coatedparticles were added to water at 90° C. Within a few seconds, theparticles dispersed into the water and the water became cloudy andoff-white. It was concluded that the protection of the soy protein andPUFA oil from the water by fat was not possible above the melting pointof the fat barrier (70° C.). Thus the protein was delivered to the waterat a temperature that caused the fat to melt.

Examples 16-24 Loading of PUFA Oil onto Solid Carriers

PUFA oil was loaded onto solid carrier particles to produce a series ofdry flowable oil products in which the oil was present as a coatedliquid. The apparatus and processes were as described in Example 1,above, with operational modifications listed in Table 3. Carrierparticles used as the solid feed material in the process includedtitanium dioxide (TiO₂, 72% w/w slurry of pigment grade material inwater, DuPont. Wilmington, Del.), CaCO₃ (Camel-CARB, Genstar StoneProducts Co. Hunt Valley, Md.), and fumed silica (Cab-O-Sil EH-5,approximately 600 m₂ surface area per gram, Cabot Corporation, Boston,Mass.). The final composition of the product of each example is given asthe percentage that is PUFA oil. TABLE 3 Drying Gas Solid PUFA oil PUFAoil PUFA gas, nozzle Solid feed feed feed oil in pressure temp. feedrate rate temp. finished Example (Kpa) (° C.) material (g/min) (g/min)(° C.) particle (%) 16 Air, 345 20 TiO₂ 410 25 22 5.8 17 Air, 345 20TiO₂ 763 74 22 8.8 18 Air, 345 20 TiO₂ 692 143 22 17.1 19 Air, 345 21CaCO₃ 604 33 22 5.5 20 Air, 345 21 CaCO₃ 628 69 22 9.9 21 Air, 345 21CaCO₃ 607 78 22 11.4 22 Air, 345 21 CaCO₃ 599 116 22 16.3 23 N₂, 414 23Cab-O-Sil 489 76 22 13.5 24 N₂, 414 22 Cab-O-Sil 218 134 22 38.1The results of these Examples demonstrate that PUFA oil can be loadedonto a variety of solid carrier particles, at levels approaching 40% ofthe final material. The resulting particles behave as if they are drypowders and offer a number of advantages for storage and handling, andfor the incorporation of PUFA-containing materials into foods andnutritional products.

Example 25 Coating of Lightly Loaded PUFA Particle with a Sucrose Layer

The PUFA-coated fumed silica particle produced in Example 23, above, wasfurther coated to produce a barrier layer of solid sucrose. Theapparatus was as described in Example 1 with the following operationalmodifications. Nitrogen was employed as the drying gas and had a nozzletemperature of 294° C. The PUFA oil-coated Cab-O-Sil particles fromExample 23 were metered into the apparatus at a rate of 487 g/min. Asolution of food grade sucrose (84% w/w in water) was metered into theapparatus at a rate of 97 g/min and at a temperature of 95° C. The drycoated particles were collected as described in Example 1. The resultantparticle possessed a first, internal layer of PUFA oil and a second,external layer of sucrose that constituted 14.4% of the finishedproduct. Such a solid coating on a PUFA material is useful as a barrierto the undesirable effects of oxidation and it improves the handlingcharacteristics of the PUFA oil-coated particles.

Example 26 Coating of Highly Loaded PUFA Particle with a Sucrose Layer

The PUFA-coated fumed silica particle produced in Example 24, above, wasfurther coated to produce a barrier layer of solid sucrose. Theapparatus was as described in Example 1 with the following operationalmodifications. Nitrogen was employed as the drying gas and had a nozzletemperature of 302° C. The PUFA oil-coated Cab-O-Sil particles fromExample 24 were metered into the apparatus at a rate of 215 g/min. Asolution of food grade sucrose (65% w/w in water) was metered into theapparatus at a rate of 71 g/min and at a temperature of 22° C. The drycoated particles were collected as described in Example 1. The resultantparticle possessed a first, internal layer of PUFA oil and a second,external layer of sucrose that constituted 17.7% of the finishedproduct. Such a solid coating on a PUFA material is useful as a barrierto the undesirable effects of oxidation and it improves the handlingcharacteristics of the PUFA oil-coated particles.

Example 27 Production of PUFA oil Particles with Multiple Coating Layersof Sucrose

PUFA oil loaded particles possessing a single sucrose barrier layer of14.4% as produced in Example 25 were used as the starting materials forpreparation of a series of multiply coated particles.

Using the product of Example 25 as the solid feed material in thecoating apparatus produced a particle containing two layers of sucrose.This was achieved by metering the product of Example 25 into theapparatus at a rate of 463 g/min. Nitrogen drying gas was at 414 KPa andwas 285° C. at the nozzle. A solution of food grade sucrose (84% w/w inwater) was metered into the apparatus at a rate of 82 g/min and at atemperature of 95° C. The dry coated particles were collected asdescribed in Example 1. The particle produced by this process consistedof a Cab-O-Sil core, an internal layer of PUFA oil, and a double layerof sucrose constituting 25.5% of the particle.

A PUFA oil particle that possessed three layers of sucrose was producedby using the doubly coated particle, produced above, as the solid feedmaterial for the coating apparatus. The PUFA particle with 30.2% sucrosewas metered into the apparatus at a rate of 634 g/min. Nitrogen dryinggas was at 414 KPa and was 277° C. at the nozzle. A solution of foodgrade sucrose (84% w/w in water) was metered into the apparatus at arate of 96 g/min and at a temperature of 95° C. The dry coated particleswere collected as described in Example 1. The particle produced by thisprocess consisted of a Cab-O-Sil core, an internal layer of PUFA oil,and a triple layer of sucrose constituting 33.9% of the particle.

It is believed that PUFA oil particles possessing multiple barrierlayers are particularly resistant to oxidative damage. Oxidation of thePUFA oil is measured using the methods available in the art. Suchmethods include the Active Oxygen Method, method Cd12-57 of the AmericanOil Chemists' Society (AOCS), and determination of the Oil StabilityIndex, AOCS method Cd 12b-92.

Example 28 Coating of a Sucrose-Coated PUFA Particle with a High MeltingTemperature Fat

A PUFA containing particle was produced with multiple layers of sucroseand an additional barrier layer comprised of high melting temperaturefat. The particle with three layers of sucrose (33.9% of the particleweight) produced in Example 27 was metered into the apparatus at a rateof 880 g/min. Nitrogen drying gas was at 414 KPa and was 216° C. at thenozzle. High melting temperature fat (Dritex, ACH Food Companies,Cordova, Tenn.) was metered at 122 g/min. to the center tube at 80° C.using the peristaltic metering pump. The dry coated particles werecollected as described in Example 1. The particle produced by thisprocess consisted of a Cab-O-Sil core, an internal layer of PUFA oil, aninternal triple layering of sucrose, and an additional barrier layer ofhigh melting fat that constituted 12.2% of the particle.

Example 29 Coating of a Sucrose-Coated PUFA Particle with Zein toProvide a Barrier to Moisture

A PUFA containing particle was produced with multiple layers of sucroseand a moisture barrier comprised of dried zein. The particle with threelayers of sucrose (33.9% of the particle weight) produced in Example 27was metered into the apparatus at a rate of 936 g/min. Nitrogen dryinggas was at 414 KPa and was 216° C. at the nozzle. A solution of zein(20% w/w in 90% EtOH/10% water, F4000 corn zein, Freeman Industries,Tuckahoe, N.Y.) was metered at 67 g/min. to the center tube at 22° C.using the peristaltic metering pump. The dry coated particles werecollected as described in Example 1. The particle produced by thisprocess consisted of a Cab-O-Sil core, an internal layer of PUFA oil, aninternal triple layering of sucrose, and an external layer of zein thatconstituted 1.4% of the particle.

Example 30 Coating of a Sucrose-Coated PUFA Particle with MultipleLayers of Zein to Provide a Barrier to Moisture

A PUFA containing particle was produced with multiple layers of sucroseand multiple layers of dried zein. The produced in Example 29, above,was metered into the apparatus at a rate of 939 g/min. Nitrogen dryinggas was at 414 KPa and was 293° C. at the nozzle. A solution of zein(20% w/w in 90% EtOH/10% water, F4000 corn zein, Freeman Industries,Tuckahoe, N.Y.) was metered at 192 g/min. to the center tube at 22° C.using the peristaltic metering pump. The dry coated particles werecollected as described in Example 1. The particle produced by thisprocess consisted of a Cab-O-Sil core, an internal layer of PUFA oil, aninternal triple layering of sucrose, a first layer of zein, and asecond, external layer of zein that constituted 5.3% of the particle.

Examples 31-35 Loading of a Liquid Drug onto a Solid Carrier

A liquid over the counter cough remedy (Vicks44®, containing one singledilute active pharmaceutical ingredient: dextromethorphan HBr (30 mgdose of active pharmaceutical ingredient in 15 ml), Procter & Gamble,Inc., Cincinnatti, Ohio) was loaded onto solid carrier particles toproduce a series of dry flowable drug products in which the drug waspresent as a coated liquid. The apparatus as shown in FIG. 1 had amixing chamber 25.4 mm in diameter and 254 mm in length with a nozzlethroat of 9.4 mm and a central liquid feed tube of 3.9 mm I.D. Theapparatus had a dual screw metering feeder (K-Tron K2VT35 dual 1.5 inch)for metering the solid particles. A peristaltic pump was fit withMasterflex® #25 tubing for metering the liquid. The coating liquid wasat ambient temperature and was metered at the feeding rates specified inTable 4 to the center tube using the peristaltic metering pump. Nitrogengas was supplied to the nozzle at 483 KPa, and was at 25° C. at thenozzle. The nitrogen gas was used to atomize the liquid drug, producinga negative pressure in the mixing zone to induce the addition of thesilica particles. Carrier particles used as the solid feed material inthe process were silica particles (Syloid®244, approximately 300 m₂surface area per gram, WR Grace and Co., Lexington, Ky.) fumed silicaparticles (Cab-O-Sil® EH-5, approximately 600 m₂ surface area per gram,Cabot Corporation, Boston, Mass.). The final composition of the productof each example is given as the weight percentage that is liquid drug.TABLE 4 Drying Gas Solid Liquid Liquid Coating gas, nozzle Solid feedfeed feed on pressure temp. feed rate rate temp. finished Example (Kpa)(° C.) material (g/min) (g/min) (° C.) particle (%) 31 N₂, 483 25 Syloid537 59 25 9.9 244 32 N₂, 483 25 Syloid 521 215 25 29.2 244 33 N₂, 483 25Cab-O-Sil 507 62.8 25 11 34 N₂, 483 25 Cab-O-Sil 498 214.2 25 30.1 35N₂, 483 25 Cab-O-Sil 513.6 932 25 64.5

The results of these Examples demonstrate that a liquid drug can beloaded onto solid carrier particles, at levels up to 65% of the finalmaterial. The resulting particles behave as if they are dry powders andoffer a number of advantages for compaction/compression, storage andhandling, and for the incorporation of liquid phase drug-containingparticles into other dosage forms.

Examples 36-37 Loading of an Oil onto a Solid Carrier

Soy oil was loaded onto solid carrier particles to produce a series ofdry flowable oil products in which the oil was present as a coatedliquid. The apparatus as shown in FIG. 1 had a mixing chamber 25.4 mm indiameter and 254 mm in length with a nozzle throat of 9.4 mm and acentral liquid feed tube of 3.9 mm I.D. The apparatus has single screwmetering feeder (AccuRate, 2.25 inch) or a dual screw metering feeder(K-Tron K2VT35 dual 1.5 inch) for metering the solid particles. Aperistaltic pump was fit with Nalgene 50 or Masterflex® #25 tubing formetering the liquid. The coating liquid was at ambient temperature andwas metered at the feeding rates specified in Table 5 to the center tubeusing the peristaltic metering pump. Nitrogen gas was supplied to thenozzle at the pressure specified in Table 5. The nitrogen gas was usedto atomize the oil, producing a negative pressure in the mixing zone toinduce the addition of the silica particles. Carrier particles used asthe solid feed material in the process were silica particles(Syloid®244, approximately 300 m₂ surface area per gram, WR Grace andCo., Lexington, Ky.). The final composition of the product of eachexample is given as the percentage that is oil. TABLE 4 Drying Gas SolidLiquid Liquid Coating gas, nozzle Solid feed feed feed on pressure temp.feed rate rate temp. finished Example (Kpa) (° C.) material (g/min)(g/min) (° C.) particle (%) 36 N₂, 552 25 Syloid 636 94 25 12.9 244 37N₂, 414 25 Syloid 562 278 25 33.1 244

The results of these Examples demonstrate that an edible oil can beloaded onto solid carrier particles, at levels up to 30% of the finalmaterial. The resulting particles behave as if they are dry powders andoffer a number of advantages for compaction/compression, storage andhandling, and for the incorporation of oil-containing particles intoother dosage forms.

Example 38 Coating of an Oil-Loaded Particle with a Gelatin Layer

The oil-coated silica particle produced in Example 36, above, wasfurther coated to produce a barrier layer of solid gelatin. Theapparatus was as described in Example 36 with the following operationalmodifications. Nitrogen was employed as the drying gas and had a nozzletemperature of 241° C. The oil-coated silica particles from Example 36was metered into the apparatus at a rate of 232 g/min. A solution offood grade gelatin (25% w/w in water) was metered into the apparatus ata rate of 41 g/min and at a temperature of 25° C. The dry encapsulatedparticles were collected as described in Example 1. The resultantparticle possessed a first, internal layer of soy oil and a second,external layer of gelatin that constituted 4.2% of the finished product.Such a solid coating on a oil material is useful as a barrier to theundesirable effects of oxidation and it improves the handlingcharacteristics of the oil-coated particles.

Example 39 Coating of an Oil-Loaded Particle with a Casein/Silica Layer

The oil-coated silica particle produced in Example 37, above, wasfurther coated to produce a barrier layer of solid casein/silica. Theapparatus was as described in Example 37 with the following operationalmodifications. Nitrogen was employed as the drying gas and had a nozzletemperature of 230° C. The oil-coated silica particles from Example 37were metered into the apparatus at a rate of 291 g/min. A suspension of5% silica (Cab-o-Sil) in a casein solution (10% w/w in water) wasmetered into the apparatus at a rate of 106 g/min and at a temperatureof 25° C. The dry encapsulated particles were collected as described inExample 1. The resultant particle possessed a first, internal layer ofsoy oil and a second, external layer of casein with Cab-o-Sil silicaparticles that constituted 5.2% of the finished product. Such a solidcoating on an oil material is useful as a barrier to the undesirableeffects of oxidation and it improves the handling characteristics of theoil-coated particles.

1. A process for coating a polyunsaturated fatty acid (PUFA)-containingcarrier particle or a PUFA matrix particle, the process comprising thesteps of: (a) metering a liquid coating material through a flowrestrictor; (b) injecting a gas stream through the flow restrictorconcurrently with step (a) to (i) atomize the liquid coating materialand (ii) create turbulent flow of the gas stream and the atomized liquidcoating material, wherein the gas stream is optionally heated; and (c)adding a PUFA-containing carrier particle or a PUFA matrix particle tothe turbulent flow region concurrently with steps (a) and (b), whereinthe PUFA-containing carrier particle or the PUFA matrix particle mixeswith the atomized liquid coating material to provide an coatedPUFA-containing carrier particle or a PUFA matrix particle.
 2. A processfor coating a liquid pharmaceutical-containing carrier particle or aliquid pharmaceutical matrix particle, the process comprising the stepsof: (a) metering a liquid coating material through a flow restrictor;(b) injecting a gas stream through the flow restrictor concurrently withstep (a) to (i) atomize the liquid coating material and (ii) createturbulent flow of the gas stream and the atomized liquid coatingmaterial, wherein the gas stream is optionally heated; and (c) adding aliquid pharmaceutical-containing carrier particle or a liquidpharmaceutical matrix particle to the turbulent flow region concurrentlywith steps (a) and (b), wherein the liquid pharmaceutical-containingcarrier particle or the liquid pharmaceutical matrix particle mixes withthe atomized liquid coating material to provide an coatedpharmaceutical-containing carrier particle or a pharmaceutical matrixparticle.
 3. The process of claim 1 or 2 wherein the carrier particle isselected from the group consisting of a protein, fumed silica, titaniumdioxide and calcium carbonate, a carbohydrate, a food particle,minerals, salts, antioxidants, solid pharmaceutical particles andlipids.
 4. The process of claim 2 wherein the pharmaceutical is selectedfrom the group consisting of nutraceuticals, vitamins, supplements,minerals, enzymes, probiotics, bronchodilators, anabolic steroids,analeptics, analgesics, proteins, peptides, antibodies, vaccines,anesthetics, antacids, antihelmintics, anti-arrthymics, antibiotics,anticoagulants, anticolonergics, anticonvulsants, antidepressants,antidiabetics, antidiarrheals, anti-emetics, anti-epileptics,antihistamines, antihormones, antihypertensives, anti-inflammatories,antimuscarinics, antimycotics, antineoplastics, anti-obesity drugs,antiprotozoals, antipsychotics, antispasmotics, anti-thrombics,antithyroid drugs, antitussives, antivirals, anxiolytics, astringents,beta-adrenergic receptor blocking drugs, bile acids, bronchospasmolyticdrugs, calcium channel blockers, cardiac glycosides, contraceptives,corticosteriods, diagnostics, digestives, diuretics, dopaminergics,electrolytes, emetics, haemostatic drugs, hormones, hormone replacementtherapy drugs, hypnotics, hypoglycemic drugs, immunosuppressants,impotence drugs, laxatives, lipid regulators, muscle relaxants, painrelievers, parasympathicolytics, parasympathicomimetics, prostagladins,psychostimulants, sedatives, sex steroids, spasmolytics, sulfonamides,sympathicolytics, sympathicomimetics, sympathomimetics, thyreomimetics,thyreostatic drugs, vasodialators, and xanthines.
 5. The process ofclaim 1 or 2 wherein the liquid coating material is selected from thegroup consisting of a natural food color, a synthetic food color, asugar, a cellulose, a biodegradable polymer, a biodegradable oligomer,an emulsifying wax, a shellac, a flavoring agent, a moisture barrier, ataste-masking agent, an odor-masking agent, hydrophobicity orhydrophilicity agents, a shelf-life extending agent, a lipid, a protein,or a mineral, ethyl cellulose, methyl cellulose, hydroxypropylcellulose,polyvinylpyrolidone, polyethylene, Aquateric, Eudragit™ (including anycommercial grade or formulations), acrylic coatings, Surelease™, bubblegum flavor, cherry flavor, grape flavor, sodium lauryl sulfate, sodiumdocusate, poly lactic acid, poly lactide glycolic acid, celluloseacetate pthalate, diluents, lactose, microcrystalline cellose, mannitol,dicalcium phosphate, starch, dextrates, sucrose, disintegrants,croscarmellose sodium, sodium starch glycolate, carbohydrate; and asbinders: hydroxypropyl cellulose, hydroxypyroylmethylcellulose,povidone, methyl cellulose, glidants/lubricants, silicon dioxide,stearic acid, a hydrocolloid, a monosaccharide, a disaccharide, anoligosaccharide, a polysaccharide, a surface modifying agent, a sugaralcohol, a poly-ol, a flow aid, an interparticle force control agent,magnesium stearate, talc, sodium stearyl fumarate, surfactants, sodiumlauryl sulfate, Tween 80, Poloxamer®, hydroxypropyl cellulose,hydroxypropylmethylcellulose, titanium dioxide, colors, polyethyleneglycols, triethyl citrate, triacetin, dibutyl sebacate andpolymethacrylates.
 6. The process of claim I wherein the polyunsaturatedfatty acid is selected from the group consisting of γ-linolenic acid(GLA), dihomo-γ-linolenic acid, arachidonic acid (ARA), docosahexaenoicacid (DHA) and/or eicosapentaenoic acid (EPA).
 7. The process of claim 1or 2 further comprising repeating steps (a)-(c) at least once whereinthe liquid coating material is the same or different or repeating steps(a)-(c) at least once using a liquid coating material which can be thesame or different from the liquid coating material.
 8. A coatedPUFA-containing carrier particle or coated PUFA matrix particle made bythe process of any of claims 1,3 5,6 or
 7. 9. A coated liquidpharmaceutical-containing carrier particle or coated liquidpharmaceutical matrix particle made by the process of any of claims 2,3, 4, 5 or
 7. 10. A food comprising a coated carrier particle or coatedmatrix particle made by the process of claims 1 or
 2. 11. A nutritionalsupplement comprising a coated carrier particle or coated matrixparticle made by the process of claim 1 or
 2. 12. A beverage comprisinga coated carrier particle or coated matrix particle made by the processof claims 1 or
 2. 13. Infant formula comprising a coated carrierparticle or coated matrix particle made by the process of claims 1 or 2.14. A pet food comprising a coated carrier particle or coated matrixparticle made by the process of claims 1 or
 2. 15. Animal feedcomprising a coated carrier particle or coated matrix particle made bythe process of claims 1 or
 2. 16. Use of a coated carrier particle orcoated matrix particle made by the process of claims 1 or 2 in producinga product selected from the group consisting of a food, nutritionalsupplement beverage, pharmaceutical formulation, infant formula, petfood or animal feed.
 17. Use of a coated carrier particle or coatedmatrix particle made by the process of claim 2 to administer apharmaceutical to a mammal by an oral, inhalable, transdermal,parenteral, buccal, nasal, vaginal, rectal, sublingual, ocular,periodontal, implantation, or topical delivery route.